Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy

Management of Cerebral Vascular Spasm in Posttraumatic Subarachnoid Hemorrhage Using Combination Therapy of Oral Nimodipine and Intravenous Milrinone: Randomized Clinical Trial

To evaluate the efficacy and safety of oral Nimodipine and IV milrinone combination therapy for management of cerebral spasm after aneurysmal subarachnoid hemorrhage.

Study Overview

• Status: Completed
• Conditions: Oral Nimodipine; Milrinone; Vascular Spasm After Traumatic Subarachnoidhaemorrhage
• Intervention / Treatment: Drug: nimodipine; Drug: Oral Nimodipine and milrinone

Detailed Description

after being informed about the study and potential risks. All patients giving written consent will be randomized by double-blind manner into 2groups each one containing 15 patients.

Group 1(n =15 ):the patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube In group 2(n =15 ): the patients will receive Oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • El Sharkia
    • Zagazig, El Sharkia, Egypt, 44519
      • Aculty of Medicine,Zagazig University
  • Zagazig, Elsharkia,egypt
    • Zagazig, Zagazig, Elsharkia,egypt, Egypt, 44519
      • Faculty of Medicine,Zagazig University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients admitted to our surgical ICU
• aged between (18-60) years old
• World Federation of Neurological Surgeons grades 1-3 Grades

Exclusion Criteria:

• Aneurysmal SAH
• SAH with Fisher Grade I and IV,
• World Federation of Neurological Surgeons grade IV & V
• No informed consent,
• peripheral vascular disease
• Cardiac disease (heart block, severe valvular stenosis, cardiomyopathothy , ejection fraction<40%), Renal impairment (serum creatinine ≥ 1.4 mg.L-1), Hemodynamic instability

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: triple H group; The patients will receive nimodipine (60 mg/4 hours) orally or via nasogastric tube from the first day of admission, then after the diagnosis of vasospasm is confirmed, Triple H therapy (hypertension, hypervolemia and hemodilution) will be started. norepnnephrine (0.01-0.2ug/kg/min) to mentain main arterial blood pressure >100mmhg and hypervolemia to maintain the CVP around 12---14 mmHg and hemodilution to maintain the haematocrit between 30% and 33%.	Drug: nimodipine; (60 mg/4 hours) orally or via nasogastric tube
ACTIVE_COMPARATOR: Milrinone group; The patients will receive oral Nimodipine (60 mg/4) will be given orally or in the gastric tube also from the first day of admission, then after the diagnosis of vasospasm is confirmed, start milrinone bolus of 0.1-0.2 mg/kg followed by 0.75mcg/k/min, if no response after 30min increase the infusion to 1-25mcg/kg/min with maintaining CVP 5:8. Norepinephrine (0.01-0.2ug/kg/min) is used only to restore the mean arterial pressure (MAP) to its previous values If there was no recurrence of symptoms after 72 h, we decreased the milrinone infusion by 0.25 mcg/kg/min every 24 or 48 h until discontinuation. If there are any recurrent of symptoms of vasospasm, the patients are placed back on the dose they were previously receiving. If required, another Milrinone bolus is administered if the patient's deficits do not revert12.	Drug: Oral Nimodipine and milrinone; Oral Nimodipine then after the diagnosis of vasospasm is confirmed, start milrinone bolus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of transcutaneous cerebral mixed oxygen saturation	by forehead bilateral interconnected adhesive probes	every 24 hours up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants having cerebral infarction (cerebral infarction incidence)	detected by computed tomography	every 48 hours up to 1 week
Number of participants restore of the previous conscious level and motor state(Percentage of drug success)	restore of the previous conscious level and motor state	1 hour after administration of milrinone and 2 hours after administration of triple H therapy
value of Glasgow coma scale	with minimum scale vlue of 3 is the worst and maximum value of 16 indicate better outcome	every 24 hours up to total days of ICU and hospital stay
Number of participants develop one of adverse events	hypotension ,bradycardia,hypotesion	after administration of the study drugs up to 30 days
Total ICU and hospital stay		up to 30 days after administration of the study drugs
mortality rate	Number of participants died within 30 day after administration of the study drugs	30 day after administration of the study drugs
value of Modified Rankin scale	Level 0: no symptoms Level 1: no significant disability, despite symptoms; able to perform all usual duties and activities Level 2: slight disability unable to perform all previous activities but able to look after own affairs without assistance Level 3: moderate disability; requires some help, but able to walk without assistance. Level 4: moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Level 5: sever disability; bedridden, incontinent and requires nursing care and attention	3,6,12 monthes after drug administration
Glasgow Outcome Scale	1. Dead: As a direct result of brain trauma, or … due to secondary complications or other complications" "2. Vegetative State: Patients who remain unresponsive and speechless…." "3. Severe Disability: The The patient is conscious but needs the assistance of another person for some activities of daily living every day.…." "4. Moderate Disability: Such a patient is able to look after himself at home, to get out and about to the shops and to travel by public transport. However, some previous activities, either at work or in social life, are now no longer possible by reason of either physical or mental deficit…." "5. Good Recovery: This indicates the capacity to resume normal occupational and social activities, although there may be minor physical or mental deficits…social outcome should be included in the assessment here, such as leisure activities and family relationships..	3,6,12 monthes after drug administration

Collaborators and Investigators

• Sponsor: Zagazig University

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 24, 2021
• Primary Completion (ACTUAL): May 23, 2022
• Study Completion (ACTUAL): May 24, 2022

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (ACTUAL): November 23, 2021

Study Record Updates

• Last Update Posted (ACTUAL): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 24, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: milrinone Oral Nimodipine
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Neuromuscular Manifestations; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Cerebrovascular Trauma; Intracranial Hemorrhage, Traumatic; Hemorrhage; Subarachnoid Hemorrhage; Spasm; Subarachnoid Hemorrhage, Traumatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Milrinone; Nimodipine
• Other Study ID Numbers: 6919

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No